The present invention relates to the pharmaceutical field, and more particularly to methods and pharmaceutical compositions for treating mammals utilizing as active agents certain novel organic heterocyclic compounds from the class known as s-triazolo-[3,4-a]-isoquinolines.
The preparation of various s-triazolo-[3,4-a]-isoquinolines is disclosed by (1) S. Naqui et al., Indian J. Chem., 3, 162-4 (1965); (2) G. S. Sidhu et al., Jour. Heterocyclic Chem., 3, 158-164 (1966); (3) J. E. Francis, U.S. Pat. No. 3,354,164 (1967); (4) H. K. Reimlinger et al., French Pat. No. 1,573,135 (1969) and (5) H. K. Reimlinger et al., Chem. Ber. 103, 1960-1981 (1970).
No pharmaceutical compositions or utility are disclosed in references (1), (2), (4) and (5) cited above. Francis (3) discloses that unsubstituted s-triazolo-[3,4-a]-isoquinoline and its 3-lower alkyl derivatives are coronary vasodilators.
The invention is particularly concerned with certain novel compounds useful in the treatment of inflammatory disorders, among which are the conditions known as arthritis.
The term "arthritis" is applied to a group of related disorders of the joints which are characterized by pain, inflammation and stiffness. Certain types of arthritis are due to specific infectious agents, but no specific cause is known for the most common type, known as rheumatoid arthritis. While this is primarily an inflammatory disease of the joints, it is sometimes accompanied by pedal edema, that is, an accumulation of fluid in the tissues of the foot. Treatment of this disease involves the administration of agents which have been found effective in reducing the pain and the inflammation. Such agents have come to be generally known as anti-inflammatory agents.
Chemical compounds having structures of varying complexity, from the structurally simple aspirin to relatively complex steroid compounds, are known to be useful anti-inflammatory agents in the treatment of arthritic and related disorders in man and other mammals. Among such recognized anti-inflammatory agents, in addition to aspirin, are the following, to which reference may be conveniently made in the Merck Index, 8th Ed., Merck & Co., Rahway, N.J. (1968): dexamethasone (p. 334), hydrocortisone (p. 542) indomethacin (p. 566), mefenamic acid (p. 648) and phenylbutazone (p. 815). However, s-triazolo-[3,4-a]-isoquinoline compounds have not heretofore been recognized as having anti-inflammatory activity.